The magnitude of the AIDS epidemic transcends that predicted just a decade ago, with an estimated 36 million people infected with HIV worldwide and about 16,000 new infections a day. Sub-Saharan Africa has accounted for the vast majority of people living with HIV and AIDS and about three-quarters of the global death toll. Whilst we continue to build the capacity and infrastructure for future HIV prevention and treatment trials in the developing world, a critical need exists for new, simple molecular diagnostic tests that account for the genetic variability of the epidemic strains and can be easily implemented at the point-of-care; a shortcoming of the commercially available assays. We hypothesize that a highly selective sequence-specific method for the colorimetric detection of HIV based on the on the optical, hybridization, and catalytic properties of gold nanoparticles conjugates will enable the rapid, simultaneous analysis of multiple clinical samples at the point-of-care, and therefore will have significant application for HIV vaccine studies and prophylactic and therapeutic trials in the developing world. In work to date, we found that detection assays based on these novel nanostructures are substantially more sensitive (3 log) and selective (0.5 log) than conventional assays that use molecular fluorophore probes, ultimately achieving the accuracy and sensitivity (100 aM) of nucleic acid sequence-based amplification. Specifically, we propose to use these novel tools to: (1) develop a highly selective sequence-specific method for the colorimetric detection of HIV DNA in cells and HIV RNA in cells and plasma in peripheral-blood based on the optical, hybridization, and catalytic properties of gold nanoparticle DNA conjugates; (2) determine the sensitivity, specificity, and quantitative range of the test by measuring the presence or absence of viral DNA in cells and the level of viral RNA in plasma in people at risk for and infected with HIV; and (3) establish proof-of-principle and validate the performance for such a diagnostic assay in the developing world by testing peripheral-blood in babies for possible mother-to-child transmission of HIV and screening the virus in peripheral-blood in their mothers for known mutations that confer nevirapine resistance in Kampala, Uganda.